Circulating antibodies to heat-shock protein 60 in Crohn's disease and ulcerative colitis

Abstract

SUMMARYHeat-shock proteins (HSPs) are highly conserved immunogenic intraeellular molecules that are induced by inflammatory mediators and may induce autoimmune phenomena in vivo. We have recently demonstrated the increased expression of HSP-60 in the coionocytes of patients with ulcerative colitis. To study further the rote of HSP-60 in inflammatory bowel disease, we have now measured antibodies to recombinant mycobacterial HSP-65 (a member ofthe HSP-60 family) in patients with Crohn's disease, ulcerative colitis, healthy volunteers and. as disease controls, patients with confirmed bacterial diarrhoea. In comparison with healthy controls {M = 20; median level of 89 ELISA units; range 24-292). serum IgA HSP-60 antibodies were elevated in Crohn's disease (n = 21; 157; 57-364; /'<005) and active ulcerative colitis (n= 16; 188; 58-373; P<00\) but not bacterial diarrhoea («= 10; 106; 51-285). Increased IgA HSP-60antibody levels in patients with inflammatory bowel disease may occur as the result of HSP release from injured gut epithelium; alternatively, increased intestinal permeability could facilitate mucosal access of luminal antigens and the generation of cross-reactive anti-bacteria! HSP antibodies.

Changes in Immunohistochemical Levels and Subcellular Localization After Therapy and Correlation and Colocalization With CD68 Suggest a Pathogenetic Role of Hsp60 in Ulcerative Colitis

“…It has been suggested that bacterial Hsp60 (GroEL) can invade the blood from its source in the intestine and induce anti-GroEL antibodies that will crossreact with the human Hsp60 and lead to autoimmune reactions in various tissues, including in the colon mucosa. [56][57][58] Similarly, GroEL could penetrate the mucosal tissue and interact with local macrophages and initiate inflammation, adding to the effect of endogenous Hsp60 freed from stressed and damaged cells. Thus, management of the intestinal flora would be of the essence in the treatment of UC.…”

Mycobacterium avium subsp. paratuberculosis in powdered infant milk: paratuberculosis in cattle - the public health problem to be solved

“…The anti-p43 antibody also identified p43, as a 28 kDa processed product in Western blots of protein extracts from MAP (Tizard et al, 1992). Mycobacterial 65 kDa heat shock proteins (Hsp65) are among the most extensively studied mycobacterial proteins, and their immunogenic characteristics have been suggested to be the basis for autoimmunization in chronic inflammatory diseases (Elsaghier et al, 1992;Stevens et al, 1992;Szewczuk and Depew, 1992).…”

Hsp60 and Hsp10 increase in colon mucosa of Crohn’s disease and ulcerative colitis

“…The participation of chaperones in the pathogenesis of autoimmune diseases, including IBD, has been postulated before (Stevens et al 1992;Ludwig et al 1999;Stahl et al 1998;Sukegawa et al 2000;Imamura et al 2005;Kamphuis et al 2005;Nara et al 2008;Puga Yung et al 2009) but information on Hsp60 and Hsp10 localization and levels in mucosal samples from CD and UC patients is scarce, or lacking in the case of Hsp10. The present work aims at filling this gap and, thus, at elucidating whether or not Hsp60 and Hsp10 should be further investigated as possible disease biomarkers useful in diagnosis and prognosis, etiologic-pathogenetic factors, or therapeutic targets in IBD.…”